Diagnosis and Severity Assessment of COPD Using a Novel Fast-Response Capnometer and Interpretable Machine Learning.

INTRODUCTION: Spirometry is the gold standard for COPD diagnosis and severity determination, but is technique-dependent, nonspecific, and requires administration by a trained healthcare professional. There is a need for a fast, reliable, and precise alternative diagnostic test. This study's aim was to use interpretable machine learning to diagnose COPD and assess severity using 75-second carbon dioxide (CO2) breath records captured with TidalSense's N-TidalTM capnometer. METHOD: For COPD diagnosis, machine learning algorithms were trained and evaluated on 294 COPD (including GOLD stages 1-4) and 705 non-COPD participants. A logistic regression model was also trained to distinguish GOLD 1 from GOLD 4 COPD with the output probability used as an index of severity. RESULTS: The best diagnostic model achieved an AUROC of 0.890, sensitivity of 0.771, specificity of 0.850 and positive predictive value (PPV) of 0.834. Evaluating performance on all test capnograms that were confidently ruled in or out yielded PPV of 0.930 and NPV of 0.890. The severity determination model yielded an AUROC of 0.980, sensitivity of 0.958, specificity of 0.961 and PPV of 0.958 in distinguishing GOLD 1 from GOLD 4. Output probabilities from the severity determination model produced a correlation of 0.71 with percentage predicted FEV1. CONCLUSION: The N-TidalTM device could be used alongside interpretable machine learning as an accurate, point-of-care diagnostic test for COPD, particularly in primary care as a rapid rule-in or rule-out test. N-TidalTM also could be effective in monitoring disease progression, providing a possible alternative to spirometry for disease monitoring.

Statistical prediction of microbial metabolic traits from genomes.

The metabolic activity of microbial communities is central to their role in biogeochemical cycles, human health, and biotechnology. Despite the abundance of sequencing data characterizing these consortia, it remains a serious challenge to predict microbial metabolic traits from sequencing data alone. Here we culture 96 bacterial isolates individually and assay their ability to grow on 10 distinct compounds as a sole carbon source. Using these data as well as two existing datasets, we show that statistical approaches can accurately predict bacterial carbon utilization traits from genomes. First, we show that classifiers trained on gene content can accurately predict bacterial carbon utilization phenotypes by encoding phylogenetic information. These models substantially outperform predictions made by constraint-based metabolic models automatically constructed from genomes. This result solidifies our current knowledge about the strong connection between phylogeny and metabolic traits. However, phylogeny-based predictions fail to predict traits for taxa that are phylogenetically distant from any strains in the training set. To overcome this we train improved models on gene presence/absence to predict carbon utilization traits from gene content. We show that models that predict carbon utilization traits from gene presence/absence can generalize to taxa that are phylogenetically distant from the training set either by exploiting biochemical information for feature selection or by having sufficiently large datasets. In the latter case, we provide evidence that a statistical approach can identify putatively mechanistic genes involved in metabolic traits. Our study demonstrates the potential power for predicting microbial phenotypes from genotypes using statistical approaches.

The potential protective effect of liraglutide on valproic acid induced liver injury in rats: Targeting HMGB1/RAGE axis and RIPK3/MLKL mediated necroptosis.

Valproic acid (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon-like peptide 1 receptor (GLP-1R) agonist that act as a novel antidiabetic drug with broad-spectrum anti-inflammatory and antioxidant effects. This study tested the protective effect of liraglutide against VPA-induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid-treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid & liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT-PCR technique. Hepatic NF-κB and TNF-α were detected immunohistochemically. Results proved that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA-hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA-induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis.

Machine diagnosis of chronic obstructive pulmonary disease using a novel fast-response capnometer.

BACKGROUND: Although currently most widely used in mechanical ventilation and cardiopulmonary resuscitation, features of the carbon dioxide (CO2) waveform produced through capnometry have been shown to correlate with V/Q mismatch, dead space volume, type of breathing pattern, and small airway obstruction. This study applied feature engineering and machine learning techniques to capnography data collected by the N-Tidal™ device across four clinical studies to build a classifier that could distinguish CO2 recordings (capnograms) of patients with COPD from those without COPD. METHODS: Capnography data from four longitudinal observational studies (CBRS, GBRS, CBRS2 and ABRS) was analysed from 295 patients, generating a total of 88,186 capnograms. CO2 sensor data was processed using TidalSense's regulated cloud platform, performing real-time geometric analysis on CO2 waveforms to generate 82 physiologic features per capnogram. These features were used to train machine learning classifiers to discriminate COPD from 'non-COPD' (a group that included healthy participants and those with other cardiorespiratory conditions); model performance was validated on independent test sets. RESULTS: The best machine learning model (XGBoost) performance provided a class-balanced AUROC of 0.985 ± 0.013, positive predictive value (PPV) of 0.914 ± 0.039 and sensitivity of 0.915 ± 0.066 for a diagnosis of COPD. The waveform features that are most important for driving classification are related to the alpha angle and expiratory plateau regions. These features correlated with spirometry readings, supporting their proposed properties as markers of COPD. CONCLUSION: The N-Tidal™ device can be used to accurately diagnose COPD in near-real-time, lending support to future use in a clinical setting. TRIAL REGISTRATION: Please see NCT03615365, NCT02814253, NCT04504838 and NCT03356288.

A Case Report of Acute Respiratory Distress Syndrome From Cannabis and Amphetamine Use.

Illicit drug usage (IDU) is a big challenge in clinical practice, with increasing incidence in the last decades. Daily, clinicians encounter a wide variety of complications related to IDU. Common infections related to illicit drugs are infective endocarditis, abscesses, osteomyelitis, pneumonia, HIV, hepatitis C, and B. Other rare complications could happen like leukoencephalopathy, IDU-related lung injury, and acute respiratory distress syndrome (ARDS) which is a severe and potentially life-threatening condition characterized by the sudden onset of respiratory failure, often necessitating mechanical ventilation. While the most common etiologies of ARDS are related to infections and sepsis, there is emerging evidence that substance abuse can also be associated with the development of ARDS with unclear mechanisms. IDU-related lung injury is a rare entity with few cases reported in the literature. Its management usually involves supportive care, including mechanical ventilation, oxygen therapy, and close monitoring of fluid balance. We present a case of a 25-year-old male presented with ARDS and multiorgan failure related to methamphetamine and cannabis abuse.

A Neonatologist-Driven Antimicrobial Stewardship Program in a Neonatal Tertiary Care Center in Oman.

OBJECTIVE: The overuse of antimicrobials in neonates is not uncommon and has resulted in a global health crisis of antibiotic resistance. This study aimed to evaluate changes associated with a neonatologist-driven antimicrobial stewardship program (ASP) in antibiotic usage. STUDY DESIGN: We conducted a pre-post retrospective cohort study in a tertiary care hospital in Oman. Neonates admitted in 2014 to 2015 were considered as the pre-ASP cohort. In 2016, a neonatologist-driven ASP was launched in the unit. The program included the optimization and standardization of antibiotic use for early- and late-onset sepsis using the Centers for Disease Control and Prevention's "broad principles," an advanced antimicrobial decision-support system to resolve contentious issues, and placed greater emphasis on education and behavior modification. Data from the years 2016 to 2019 were compared with previous data. The outcome of interest included days of therapy (DOT) for antimicrobials. Baseline characteristics and outcomes were compared using standard statistical measures. RESULTS: The study included 2,098 neonates in the pre-ASP period and 5,464 neonates in the post-ASP period. There was no difference in baseline characteristics. The antibiotic use decreased from 752 DOT per 1,000 patient-days (PD) in the pre-ASP period to 264 DOT in the post-ASP period (64.8% reduction, p < 0.001). The proportion of neonates who received any antibiotics declined by 46% (pre-ASP = 1,161/2,098, post-ASP = 1,676/5,464). The most statistically significant reduction in DOT per 1,000 PD was observed in the use of cefotaxime (82%), meropenem (74%), and piperacillin-tazobactam (74%). There was no change in mortality, culture-positive microbial profile, or multidrug-resistant organism incidence in the post-ASP period. CONCLUSION: Empowering frontline neonatologists to drive ASPs was associated with a sustained reduction in antibiotic utilization. KEY POINTS: · Overuse of antimicrobials is not uncommon in neonatal intensive care units.. · ASPs and infection control and prevention measures may help in decreasing antibiotic consumption and culture-positive sepsis.. · Empowering frontline neonatologists resulted in a sustained decrease in antimicrobial use without extra resources or financial burden..

The Impact of SKP2 Gene Expression in Chronic Myeloid Leukemia.

Introduction: The prognosis of chronic myeloid leukemia (CML) patients has been dramatically improved with the introduction of imatinib (IM), the first tyrosine kinase inhibitor (TKI). TKI resistance is a serious problem in IM-based therapy. The human S-phase kinase-associated protein 2 (SKP2) gene may play an essential role in the genesis and progression of CML. Aim of the study: We try to explore the diagnostic/prognostic impact of SKP2 gene expression to predict treatment response in first-line IM-treated CML patients at an early response stage. Patients and methods: The gene expression and protein levels of SKP2 were determined using quantitative RT-PCR and ELISA in 100 newly diagnosed CML patients and 100 healthy subjects. Results: SKP2 gene expression and SKP2 protein levels were significantly upregulated in CML patients compared to the control group. The receiver operating characteristic (ROC) analysis for the SKP2 gene expression level, which that differentiated the CML patients from the healthy subjects, yielded a sensitivity of 86.0% and a specificity of 82.0%, with an area under the curve (AUC) of 0.958 (p < 0.001). The ROC analysis for the SKP2 gene expression level, which differentiated optimally from the warning/failure responses, yielded a sensitivity of 70.59% and a specificity of 71.21%, with an AUC of 0.815 (p < 0.001). Conclusion: The SKP2 gene could be an additional diagnostic and an independent prognostic marker for predicting treatment responses in first-line IM-treated CML patients at an early time point (3 months).

Does Hepatitis C Virus Treatment by Directly Acting Antivirals Obligate Shifting Patients with Type 2 Diabetes from Oral Hypoglycemic Drugs to Insulin Therapy?

Purpose: The aim of the present work was to investigate whether hepatitis C virus treatment by directly acting antivirals obligate shifting patients with type 2 diabetes from oral hypoglycemic drugs to insulin therapy. Methods: This was a prospective study including 92 treatment-naïve patients with chronic hepatitis C virus infection and type 2 diabetes who were eligible for treatment with directly acting antivirals (sofosbuvir + daclatasvir ± ribavirin). Patients in the study were divided into two groups; group 1 included 22 patients on insulin therapy and group 2 included 70 patients on oral antidiabetic medications. Patients were advised to keep on their anti-diabetic treatment. Results: All our patients achieved sustained virologic response with significantly lower HbA1c 12 weeks after the end of therapy (p. values 0.001 for group 1 and group 2). There was no statistically significant difference in HbA1c level post-treatment between both groups (p. value 0.352). Conclusion: Achievement of sustained virologic response using interferon free, directly acting antivirals-based regimen was associated with significantly lower HbA1c 12 weeks after the end of therapy. The type of treatment used for type 2 diabetes (oral drugs or insulin) did not affect improved glycemic control observed after achieving sustained virologic response.

Molecular epidemiology of lumpy skin disease outbreak in Odisha, India.

Lumpy skin disease virus (LSDV) is the causative agent of lumpy skin disease (LSD) which is a member of Capripoxvirus. It is an economically critical transboundary disease affecting cattle. This study records an LSD outbreak in Ganjam district of Odisha, India during August 2020. The epidemiological data were analysed and LSDV was genetically characterized. Out of the 452 animals clinically examined (59 farms), 63 animals were clinically affected with LSD, with a total morbidity rate of 13.93%. The morbidity rates in the surveyed villages (n = 10) varied from 5.55 to 21.62%. The multivariable logistic regression analysis showed that grazing of animals (P = 0.013; OR: 2.04; 95% CI: 1.16-3.57) and age of cows > 3 years old (P = 0.001; OR: 2.90; 95% CI: 1.65- 5.07) were potential risk factors for the presence of LSD. Out of the 53 clinically suspected animals' samples, 18 samples (33.96%) were found positive for both the P32 and F genes of Capripoxvirus by PCR. Phylogenetic analysis of the P32 gene of LSDV (MW147486) showed 100% similarity with other isolates from India, Bangladesh, Egypt and Saudi Arabia. Additionally, phylogenetic analysis of the F gene of LSDV (MW147485) revealed a similarity of 97.99%, with Odisha India (MT074110) isolate and located in the same cluster with other Indian isolates.

Non-ulcerogenic pyrazolyl 2-hydroxychalcones and pyrazolylpyrazolines derived from naturally existing furochromone (khellin): semi-synthesis, docking study and anti-inflammatory activity.

Novel pyrazolyl 2-hydroxychalcone derivatives 3a-e and pyrazolylpyrazoline derivatives 4a-e and 5a-j derived from the naturally existing furochromone (Khellin) were synthesized and evaluated for their in vivo anti-inflammatory activity. Most of the synthesized compounds showed better or comparable activity to that of Diclofenac as reference drug. Twelve compounds were evaluated for their ulcerogenic potential and exhibited no ulcerogenic effect. In addition compounds 3c, 5c and 5h as examples showed PGE2 inhibition % 88.86, 65.87 and 44.06, respectively and TNFα inhibition % 48.62, 31.11 and 16.02, respectively in rat serum samples. Compounds 3c, 5c, 5h and Celecoxib were subjected to in vitro COX-1 and COX-2 inhibition assay, showed selectivity index 45.04, 102.04, 131.58 and 185.18, respectively. The computational finding supported those of in vitro, where the pyrazolylpyrazolines interacted with the COX-2 enzyme in a similar orientation to that of Celecoxib, while chlacones were found to exhibit similar orientation to that of Diclofenac.

Epidemiological, bacteriological and molecular studies on caseous lymphadenitis in sheep of Dakhlia, Egypt.

Caseous lymphadenitis (CLA) is a chronic and insidious disease that mainly affects small ruminants and caused by Corynebacterium pseudotuberculosis (C. pseudotuberculosis). The aims of this research were to identify C. pseudotuberculosis by PCR from pyogenic lesions, to study the phylogenetic analysis of C. pseudotuberculosis and to detect the prevalence based on the detected superficial lesions of CLA in Dakahlia governorate, Egypt. Out of 3471 clinically examined animals, 129 (3.71%) animals were affected with CLA. The isolation rate of C. pseudotuberculosis in abscess of sheep was 45.74% (59/129). Out of 129 samples examined by PCR assay, 63 (48.83%) were positive phospholipase D (PLD) indicated at fragment size 203 bp. This is the first phylogenetic analysis study of C. pseudotuberculosis isolate in Egypt which was isolated from infected sheep. Nucleotide sequence identity data demonstrated that C. pseudotuberculosis PLD gene (MW187942) Dakahlia share homology 99.01%, 98.83 and 98.48% with Zagazig, Egypt (MN867024), Tamil nadu, India (MG720636) and Sudan (MG692441), respectively. In conclusion, this study provided information on the molecular detection and phylogeny of C. pseudotuberculosis in Egypt. Findings of this study can be conducted in other CLA endemic countries with similar animal breeding practices in the Middle East and developing countries.

Rebooting atrial fibrillation ablation in the COVID-19 pandemic.

PURPOSE: Catheter ablation procedures for atrial fibrillation (AF) were significantly curtailed during the peak of coronavirus disease 2019 (COVID-19) pandemic to conserve healthcare resources and limit exposure. There is little data regarding peri-procedural outcomes of medical procedures during the COVID-19 pandemic. We enacted protocols to safely reboot AF ablation while limiting healthcare resource utilization. We aimed to evaluate acute and subacute outcomes of protocols instituted for reboot of AF ablation during the COVID-19 pandemic. METHODS: Perioperative healthcare utilization and acute procedural outcomes were analyzed for consecutive patients undergoing AF ablation under COVID-19 protocols (2020 cohort; n=111) and compared to those of patients who underwent AF ablation during the same time period in 2019 (2019 cohort; n=200). Newly implemented practices included preoperative COVID-19 testing, selective transesophageal echocardiography (TEE), utilization of venous closure, and same-day discharge when clinically appropriate. RESULTS: Pre-ablation COVID-19 testing was positive in 1 of 111 patients. There were 0 cases ablation-related COVID-19 transmission and 0 major complications in either cohort. Pre-procedure TEE was performed in significantly fewer 2020 cohort patients compared to the 2019 cohort patients (68.4% vs. 97.5%, p <0.001, respectively) despite greater prevalence of persistent arrhythmia in the 2020 cohort. Same-day discharge was achieved in 68% of patients in the 2020 cohort, compared to 0% of patients in the 2019 cohort. CONCLUSIONS: Our findings demonstrate the feasibility of safe resumption of complex electrophysiology procedures during the COVID-19 pandemic, reducing healthcare utilization and maintaining quality of care. Protocols instituted may be generalizable to other types of procedures and settings.

Time to diagnosis of acute complications after cardiovascular implantable electronic device insertion and optimal timing of discharge within the first 24 hours.

BACKGROUND: More than 3 million cardiovascular implantable electronic devices (CIEDs) are implanted annually. There are minimal data regarding the timing of diagnosis of acute complications after implantation. It remains unclear whether patients can be safely discharged less than 24 hours postimplantation. OBJECTIVE: The purpose of this study was to determine the precise timing of acute complication diagnosis after CIED implantation and optimal timing for same-day discharge. METHODS: A retrospective cohort analysis of adults 18 years or older who underwent CIED implantation at a large urban quaternary care medical center between June 1, 2015, and March 30, 2020, was performed. Standard of care included overnight observation and chest radiography 6 and 24 hours postprocedure. Medical records were reviewed for the timing of diagnosis of acute complications. Acute complications included pneumothorax, hemothorax, pericardial effusion, lead dislodgment, and implant site hematoma requiring surgical intervention. RESULTS: A total of 2421 patients underwent implantation. Pericardial effusion or cardiac tamponade was diagnosed in 13 patients (0.53%), pneumothorax or hemothorax in 19 patients (0.78%), lead dislodgment in 11 patients (0.45%), and hematomas requiring surgical intervention in 5 patients (0.2%). Of the 48 acute complications, 43 (90%) occurred either within 6 hours or more than 24 hours after the procedure. Only 3 acute complications identified between 6 and 24 hours required intervention during the index hospitalization (0.12% of all cases). CONCLUSION: Most acute complications are diagnosed either within the first 6 hours or more than 24 hours after implantation. With rare exception, patients can be considered for discharge after 6 hours of appropriate monitoring.

Role of Selexipag in Chronic Obstructive Pulmonary Disease (COPD) Patients With Out-of-Proportion Pulmonary Hypertension.

Pulmonary hypertension (PH) in patients with chronic obstructive pulmonary disease (COPD) is associated with an increase in the risk of COPD exacerbation, increased hospitalization, and worse survival in this patient population. No specific treatment is available for PH in COPD. However, reported out-of-proportion PH may benefit from a certain type of treatment. This study shows that the use of selexipag in the treatment of out-of-proportion PH in COPD patients was associated with an improvement in functional status evaluated by a six-minute walk test (6MWT) and a mean pulmonary artery pressure at 6 +/- 2 months of treatment.

Transplacental transmission of Theileria annulata in cattle confirmed by molecular techniques.

Theileria annulata (T. annulata) is a tick-borne apicomplexan parasite affecting ruminants and causes severe economic loss. The present paper reports the vertical transmission of T. annulata in a three day old crossbred Jersey calf. Molecular diagnosis of tropical theileriosis was done by PCR, cloning, sequencing and phylogenetic analysis of isolated parasites. Calf showed very low hematocrit value (HCT) (17.82%), red blood cells count (RBC) count (6.9 × 106/µL), and hemoglobin concentration (Hb) (6.6 g/dL). Phylogenetic analysis of Tams 1 gene showed that T. annulata Khorda isolate (MW123091) shared 99.23%, 99.23% and 99.11% nucleotide homology with Puri, India (MN818858), Bahrain (AF214797) and Hyderabad, India (MK034702), respectively. This is the first study in Odisha, India to give an insight into the molecular detection, phylogeny and hematological analysis of T. annulata infected crossbred Jersey calf which got the infection through transplacental transmission.

Rabies in a Sand Cat (Felis margarita) in Saudi Arabia: One Health Implications.

We report a case of rabies in a sand cat, Felis margarita, from Saudi Arabia. This incident suggests hitherto undocumented spillover infection in this species. Our report highlights the shortcomings of passive reporting, necessity of wildlife surveillance, and the need for a comprehensive One Health approach to disease prevention and control.

Molecular detection of Theileria annulata infection in cattle by conventional PCR and quantitative real time PCR in India.

Theileria annulata (T. annulata) is a tick-borne apicomplexan parasite that affects bovine. It is endemic in many tropical and subtropics areas, including Odisha, India. The objective of this study is to identify T. annulata infection in the peripheral blood of cattle as a biological sample by conventional PCR (cPCR) and quantitative PCR (qPCR). The phylogenetic analysis was done using the T. annulata merozoite surface antigen (Tams 1) gene. Out of 552 samples of examined blood smears by microscopy, 454 (82.24%) animals were positive for Theileria species. Out of 454 samples, 96 samples were further examined by both cPCR and qPCR, 52 samples (54.16%) were found positive for T. annulata in both PCR methodologies. Phylogenetic analysis revealed that T. annulata Odisha isolate was closely related to T. annulata Uttarakhand, India isolate (KM061799) and Hyderabad, India isolate (MK034702) with Nucleotide sequence identity 95.36%, 95.25%, respectively. This is the first study to detect T. annulata by qPCR in Odisha and supported that both PCR techniques were equally effective for the detection of Tams 1 gene of T. annulata in cattle's blood.

Perioperative management of arteriovenous malformation guided by integrated evaluation of hemodynamics.

We aimed to demonstrate the value of monitoring infants with arteriovenous malformation (AVM) during endovascular embolization with integrated evaluation of hemodynamics (IEH) and guiding decisions according to the underlying pathophysiology. This is a retrospective analysis of the perioperative hemodynamics data for 2 complex cases of AVM transferred to Khaula Hospital in Oman for interventional management. We described the value of novel physiological insights gained from comprehensive IEH and provided a systematic approach to the perioperative management. Postoperative targeted neonatal echo (TNE) was used to guide the weaning of the cardiovascular medications within 24 h. Both cases showed significant right ventricle (RV) volume overload before surgery. Narrowing of the pulse pressure (PP) during or after endovascular embolization was used as a marker of compromised systemic blood flow in real time followed by an assessment by TNE to guide the appropriate therapy.Conclusion: Integrated evaluation of hemodynamics is helpful to guide perioperative physiologic-based management of AVM. What is Known: • The preoperative management of hemodynamic compromise due to AVM has been described in many articles. • Perioperative management of AVM and related hemodynamics is a challenge to the intensive care team. What is New: • Integrated evaluation of hemodynamics is a comprehensive assessment and helpful in understanding the underlying physiologic changes during intervention with AVM. • This integrated evaluation can lead to physiologic-based medical recommendation with subsequent improvement.